Inhalation is a convenient administration route for therapeutic agents that overcomes many of the drawbacks of oral administration, such as slow drug onset and first-pass metabolism plus it can be used with patients that suffer from nausea, emesis, or dysphagia. Inhalation of a salt form of a therapeutic agent usually produces rapid systemic adsorption exemplified by an early, high peak in plasma concentration that then drops off rapidly over time. In many situations, such a pharmacokinetic profile is desirable, but in other instances, a different pharmaceutical profile would better fit the clinical need. For instance, with migraines sufferers, an ideal pharmaceutical composition would provide fast initial relief of symptoms by producing an early high peak in plasma concentration and that additionally maintains a relatively high plasma concentration over time to prevent relapse. A pharmaceutical composition with this pharmacokinetic profile would represent an important therapeutic breakthrough for the treatment of migraines. Similarly, other indications such as emesis would benefit from the ability to tailor the pharmacokinetic profile of an inhalable therapeutic agent.
There exists a need to be able to engineer inhalable pharmaceutical formulations so that the pharmacokinetic profiles more closely fit clinical requirements. The discovery that pharmacokinetic profiles can be engineered based on the careful selection of the chemical and physical properties of inhalable particles meets this need.